Chronic Obstructive Pulmonary Disease, Pulmonary Hypertension
Conditions
Keywords
Treprostinil, Lung Diseases, Hypertension, Vascular Diseases
Brief summary
This open-label study will evaluate the safety of continued therapy with inhaled treprostinil in participants who have completed Study RIN-PH-304 (NCT03496623). This study hypothesizes that long-term safety findings will be similar to those observed in the randomized, placebo-controlled, double-blind, adaptive study 'A Phase 3, Randomized, Placebo-controlled, Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease (PH-COPD)(RIN-PH-304).
Detailed description
This is a multi-center, open-label study for eligible participants who completed all scheduled study visits during the Treatment Period of Study RIN-PH-304. Participants who provide informed consent for this open-label extension study on or prior to the final study visit of RIN-PH-304 may participate in the study, provided all other eligibility criteria are met. The RIN-PH-304 final study visit and the RIN-PH-305 Enrollment Visit will occur on the same day. All participants will reinitiate inhaled treprostinil at 3 breathes (18 micrograms \[mcg\]) 4 times daily (QID) during waking hours. Study drug doses should be maximized to tolerability throughout the study, and dose titrations should occur as rapidly as possible (as directed by the Investigator) with a target dosing regimen of 15 breaths QID or the maximum tolerated dose.
Interventions
Inhaled treprostinil solution per dose and schedule specified in the arm
Sponsors
United Therapeutics
Lung Biotechnology PBC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This trial is not blinded. All participants will begin titration of study drug once all entry criteria have been met.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant voluntarily gives informed consent to participate in the study. 2. Participant completed Study RIN-PH-304. 3. Women of childbearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, \[less than 1% per year\], such as approved hormonal contraceptives, barrier methods \[such as condom or diaphragm\] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. 4. Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug.
Exclusion criteria
1. The participant is pregnant or lactating. 2. The participant was prematurely discontinued from Study RIN-PH-304. 3. The participant is intolerant to inhaled prostanoid therapy. 4. The participant is unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device). 5. The participant is scheduled to receive another investigational drug, device, or therapy during the course of this study. 6. Any other clinically significant illness or abnormal laboratory value(s) that, in the opinion of the Investigator, might adversely affect the interpretation of the study data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 4 years | An adverse event (AE) can be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent was defined as any AE occurring/worsening at any time after a participant was exposed to study drug up until 7 days after the last dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in 6-Minute Walk Distance (6MWD) | Baseline, Week 6 | 6MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6-minute walk test (6MWT) was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. |
| Change From Baseline to Week 6 in Borg Dyspnea Score | Baseline, Week 6 | The Borg Dyspnea Score was a 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT. |
| Change From Baseline to Week 6 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Baseline, Week 6 | The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function. Improvement is defined as a decrease in the NT-proBNP plasma concentration. |
Countries
Israel, Italy, United States
Participant flow
Pre-assignment details
41 participants, who either successfully completed or were administratively terminated due to the COVID-19 pandemic from Study RIN-PH-304 (NCT03496623), chose to enroll in Study RIN-PH-305 (NCT03794583) open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil Participants received up to 90 μg of treprostinil for inhalation QID, for up to 4 years | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Treprostinil |
|---|---|
| Age, Continuous | 68.24 years STANDARD_DEVIATION 7.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 41 |
| other Total, other adverse events | 22 / 41 |
| serious Total, serious adverse events | 13 / 41 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) can be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent was defined as any AE occurring/worsening at any time after a participant was exposed to study drug up until 7 days after the last dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to 4 years
Population: Safety population included all participants who received at least 1 dose of inhaled treprostinil.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treprostinil | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 35 Participants |
Secondary
Change From Baseline to Week 6 in 6-Minute Walk Distance (6MWD)
6MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6-minute walk test (6MWT) was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded.
Time frame: Baseline, Week 6
Population: All participants set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Change From Baseline to Week 6 in 6-Minute Walk Distance (6MWD) | Baseline | 226.5 meters | Standard Deviation 88.91 |
| Treprostinil | Change From Baseline to Week 6 in 6-Minute Walk Distance (6MWD) | Change at Week 6 | 15 meters | Standard Deviation 43.58 |
Secondary
Change From Baseline to Week 6 in Borg Dyspnea Score
The Borg Dyspnea Score was a 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT.
Time frame: Baseline, Week 6
Population: All participants set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Change From Baseline to Week 6 in Borg Dyspnea Score | Baseline | 5.03 score on a scale | Standard Deviation 2.57 |
| Treprostinil | Change From Baseline to Week 6 in Borg Dyspnea Score | Change at Week 6 | 0.38 score on a scale | Standard Deviation 1.94 |
Secondary
Change From Baseline to Week 6 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function. Improvement is defined as a decrease in the NT-proBNP plasma concentration.
Time frame: Baseline, Week 6
Population: All participants set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Change From Baseline to Week 6 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Change at Week 6 | -155.55 nanogram/liter (ng/L) | Standard Deviation 558.96 |
| Treprostinil | Change From Baseline to Week 6 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Baseline | 1279.6 nanogram/liter (ng/L) | Standard Deviation 2080.19 |